Cytochrome P450

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Introduction

Cytochromes P450 (CYPs) are a superfamily of proteins which in the human body are responsible of the metabolism of endogenous and exogenous chemicals, including cannabinoids. CYPs metabolize drugs mainly in the liver, making them specially relevant when cannabinoids are used through the oral route of administration. cannabinoids are metabolized by CYPs but they can also induce (increase activity) or inhibit the action of CYPs, modulating their metabolic action in other drugs. Co-administration of cannabinoids and other drugs can modulate their levels in blood, affecting their therapeutic properties. More research is needed to understand how cannabinoids interact with other drugs.

Most THC (and presumably most plant cannabinoids) is degraded by Cyp2C9 in the liver.

Vice versa, most cannabinoids and CBD in particular have the ability to inhibit Cyp enzymes to varying degrees.

As Cyp enzymes are not only responsible for the metabolism of cannabinoids but also of all medical drugs and many components of our general metabolism these Cannabinoid-Cyp interactions can have a large impact on our metabolism and well being.

Given the amount of circulating cannabinoids, typically nanomolar, and their apparent affinity for Cyp enzymes, typically low-micromolar, cannabinoids are normally not expected to exert a strong effect on other metabolic events. However, Cyp enzymes are highly polymorphic with multiple alleles in the general population, each with slightly different functional characteristics. Such polymorphisms do not only help determine which diseases a person is likely to develop but also how they respond to cannabinoids and/or other therapeutic drugs.

For instance, although CBD is a relatively strong inhibitor of Cyp2D6, this effect probably occurs at relatively high doses (200mg or higher, estimated from: (Yamaori et al., 2011)).

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